Ethylnitrosourea (ENU) and methylnitrosourea (MNU) are potent chemical carcinogens which selectively induce tumors in the nervous system. These tumors have striking histological, histochemical and biochemical similarities to the tumors encountered in human pathology. The mechanism of action of ENU and MNU in the rat nervous system will be investigated. The fate of the transplacentally administered (1-C14) - ENU will be followed in different subcellular membranes of brain and liver of the fetus and the mother. The incorporation of radioactivity into nucleic acids, proteins and lipids will be investigated. Biochemical experiments are planned to determine whether the proliferating cells are more susceptible to this alkylating agent than fully differentiated and resting cells. Lipids are structural components of all cell membranes. Alterations in the lipid components have been observed in the transformed cells. The composition, content and in vivo and in vitro metabolism of lipids such as phospholipids, glycolipids, sterols and their fatty acid moieties will be studied in neurotumors induced by ENU and MNU. Different histological types of tumors will be examined. The results will be compared with those obtained with the corresponding areas of normal brain as well as enriched preparations of astroglia, oligodendroglia and neurons. Elevation in the activities of certaan lysosomal enzymes in neurotumors have been reported. Detailed studies are planned to investigate alteration in the activities of several hydrolytic enzymes in different histological types of neurotumors. Various 'artificial' and 'natural' substrates will be used to determine the hydrolytic enzyme activities. Certain lipids such as galactocerebrosides and sulfatides are predominantly localized in myelin. The synthesis of these lipids in transformed cell tumors, oligodendroglioma and neurinoma will be studied.